The study of the host's immune response to cancer avoids the difficulties encountered in the use of xenoantisera and may identify antigens of physiological relevance. We have confirmed the work of others in identifying polyclonal autologous antibody in the sera of one-third of patients studied, with specificity for individually restricted and common melanoma antigens. However, because of the low incidence and titer of these antibodies we have turned to immune complexes as a new source of host-derived serological agents. Acid dissociation and ultrafiltration of serum has resulted in enhanced autologous reactivity in 9 of 10 cases studied. Three enhanced serum have revealed a specificity for common tumor antigens. It would appear that immune complexes provide a readily accessable source for the isolation and study of physiologically relevant antigen and antibody. Antibody derived from immune complexes may produce a reagent with potential diagnostic and therapeutic applications. Serial studies of individual autologous and allogeneic systems will allow correlation between immune complexes, antibody reactivity and clinical course. Serologic studies will be performed utilizing sensitive microserological assays. Analysis of immune complexes will be carried out with a variety of methods (Clq, Raji cell, zone electrophoresis), because of the imperfect nature of the assays currently available. Immunochemical analysis will involve isolation of cell surface antigens from whole cell extracts and acid dissociated ultrafiltrate. Subsequent analysis will be undertaken by polyacrylamide gel electrophoresis with blotting and detection using double antibody. In addition, antigen detected will be subjected to sequence analysis on a gas phase sequenator. Antigen isolated from immune complexes will be characterized by immunochemical analysis and may provide an understanding of one basis of immunosuppression by melanoma and other tumors.